Effect of maternal infection on stillbirths and early neonatal deaths: nested case-control studies in pregnancy cohorts in East Africa

BackgroundReducing perinatal deaths is a priority, but data on maternal infectious causes are sparse in low- and middle-income countries where the burden is highest. We aimed to describe maternal infections at delivery and their association with perinatal death in Kilifi County Hospital (KCH), Kenya and Hiwot Fana Comprehensive Specialised Hospital (HFCSH), Ethiopia. MethodsWe investigated 642 mothers delivering stillbirths/newborns dying in the first 24h after birth (cases) and 855 mothers with newborns surviving >24h (controls), from well-characterised pregnancy cohorts in a nested case-control design in KCH (2011-17) retrospectively and HFCSH (2019-20) prospectively. We tested maternal blood for infection at delivery using molecular methods with 60 PCR targets (TaqMan Array Cards, TAC). In HFCSH, vagino-rectal swabs (VRS) and oropharyngeal swabs (OPS) were also tested, with 28 and 42 PCR targets respectively, along with conventional microbiological testing. We tested associations between maternal infection and perinatal death for each site, separately, and combined, and adjusted for potential confounders. We did a sensitivity analysis using only controls with good pregnancy outcomes in KCH. Where appropriate, we calculated the population attributable fraction (PAF). ResultsIn HFCSH, maternal bacteraemia was associated with perinatal death (adjusted odds ratio aOR3.7 [1.5-9.2]). In KCH, bacterial detection in maternal blood was associated with perinatal death (aOR2.7 [1.2-6.0]), but only in sensitivity analysis. Escherichia coli/Shigella was associated with perinatal death when cultured/detected in blood (aOR2.6 [1.1-6.3]) across sites. Though infrequent, Bordetella sp. was associated with perinatal death (OR4.9[1.1-23.0]) on OPS in HFCSH. No other individual infections were associated with perinatal death. The PAF for perinatal deaths among hospital deliveries was 6.1% (4.0%-8.2%) for maternal bacteraemia in HFCSH and 4.9% (2.6%-7.2%) for bacterial detection in KCH. ConclusionsMaternal bacterial infection is associated with perinatal death in high-burden settings, and in our study accounted for around 5% of perinatal deaths in hospital deliveries. The study was underpowered to detect species-specific infections associated with perinatal death. FundingWellcome (205184)